Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model

Precipitation controls on nutrient budgets in subtropical and tropical forests and the implications under changing climate

Biological, geological and hydrological drivers collectively control forest biogeochemical cycling. However, based on a close examination of recent literature, we argue that the role of hydrological control particularly precipitation on nutrient budgets is significantly underestimated in subtropical and tropical forests, hindering our predictions of future forest nutrient status under a changing climate in these systems. To test this hypothesis, we analyzed two decades of monthly nutrient input and output data in precipitation and streamwater from a subtropical forested watershed in Taiwan, one of the few sites that has long-term nutrient input-output data in the tropics and subtropics. The results showed that monthly input and output of all ions and budgets (output – input) of most ions were positively correlated with precipitation quantity and there was a surprisingly greater net ion export during the wet growing season, indicating strong precipitation control on the nutrient budget. The strong precipitation control is also supported by the divergence of acidic precipitation and near neutral acidity of streamwater, with the former being independent from precipitation quantity but the latter being positively related to precipitation quantity. An additional synthesis of annual precipitation quantity and nutrient budgets of 32 forests across the globe showed a strong correlation between precipitation quantity and nutrient output-input budget, indicating that strong precipitation control is ubiquitous at the global scale and is particularly important in the humid tropical and subtropical forests. Our results imply that climate change could directly affect ecosystem nutrient cycling in the tropics through changes in precipitation pattern and amount

Long-term Clinical Outcomes Following Elective Stent Implantation for Unprotected Left Main Coronary Artery Disease

Background/PurposePercutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease.MethodsA total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included.ResultsDuring the follow-up period of 45 ± 35 months (range: 1–137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11–4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27–22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63–11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65–9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16–0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43–24.80) could predict the composite endpoint, including target vessel revascularization and total mortality.ConclusionWe showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality

The impact of neglecting ice phase on cloud optical depth retrievals from AERONET cloud mode observations

Clouds present many challenges to climate modelling. To develop and verify the parameterisations needed to allow climate models to represent cloud structure and processes, there is a need for high-quality observations of cloud optical depth from locations around the world. Retrievals of cloud optical depth are obtainable from radiances measured by Aerosol Robotic Network (AERONET) radiometers in “cloud mode” using a two-wavelength retrieval method. However, the method is unable to detect cloud phase, and hence assumes that all of the cloud in a profile is liquid. This assumption has the potential to introduce errors into long-term statistics of retrieved optical depth for clouds that also contain ice. Using a set of idealised cloud profiles we find that, for optical depths above 20, the fractional error in retrieved optical depth is a linear function of the fraction of the optical depth that is due to the presence of ice cloud (“ice fraction”). Clouds that are entirely ice have positive errors with magnitudes of the order of 55 % to 70 %. We derive a simple linear equation that can be used as a correction at AERONET sites where ice fraction can be independently estimated. Using this linear equation, we estimate the magnitude of the error for a set of cloud profiles from five sites of the Atmospheric Radiation Measurement programme. The dataset contains separate retrievals of ice and liquid retrievals; hence ice fraction can be estimated. The magnitude of the error at each location was related to the relative frequencies of occurrence in thick frontal cloud at the mid-latitude sites and of deep convection at the tropical sites – that is, of deep cloud containing both ice and liquid particles. The long-term mean optical depth error at the five locations spans the range 2–4, which we show to be small enough to allow calculation of top-of-atmosphere flux to within 10 % and surface flux to about 15 %

Cloud optical depth retrievals from the Aerosol Robotic Network (AERONET) cloud mode observations

Cloud optical depth is one of the most poorly observed climate variables. The new “cloud mode” capability in the Aerosol Robotic Network (AERONET) will inexpensively yet dramatically increase cloud optical depth observations in both number and accuracy. Cloud mode optical depth retrievals from AERONET were evaluated at the Atmospheric Radiation Measurement program’s Oklahoma site in sky conditions ranging from broken clouds to overcast. For overcast cases, the 1.5 min average AERONET cloud mode optical depths agreed to within 15% of those from a standard ground‐based flux method. For broken cloud cases, AERONET retrievals also captured rapid variations detected by the microwave radiometer. For 3 year climatology derived from all nonprecipitating clouds, AERONET monthly mean cloud optical depths are generally larger than cloud radar retrievals because of the current cloud mode observation strategy that is biased toward measurements of optically thick clouds. This study has demonstrated a new way to enhance the existing AERONET infrastructure to observe cloud optical properties on a global scale

Investigation of functional relationship between FIN219 and photomorphogenic mutants in Arabidopsis

phyA (phytochrome A)為阿拉伯芥中遠紅光的接受體，在遠紅光中可抑制下胚軸延長，phyA的N端帶有一個可感受光訊息的色基，C端含有可傳遞訊息給下游基因的kinase區域。FIN219 (far-red insensitive 219)基因參與遠紅光下游的訊息傳遞，在遠紅光中fin219突變體具有下胚軸延長的外表型，FIN219的N端及C端各有一個coiled-coil區域可能與蛋白質間的交互作用有關；由分析得知，FIN219的N端和phyA的GAF區域其胺基酸序列上存在43%的相似性。GH3-10為阿拉伯芥中GH3-like基因家族中之ㄧ員，胺基酸序列親源性分析指出，GH3-10與FIN219有47%的相似性。因此欲探討GH3-10、phyA和FIN219之間的訊息傳遞與調控關係及PHYA其N端或C端的功能與作用機制。 由酵母菌雙雜合分析指出，FIN219與GH3-10的全長和phyA的C端有交互作用，上位性基因分析指出FIN219作用於phyA的下游，並且FIN219的表現僅在遠紅光phyA突變株中有明顯下降，暗示著FIN219蛋白質含量的多寡取決於植物在遠紅光下phyA是否存在。建構大量表現PHYA其N端或C端的轉殖株，觀察到在野生型背景中的轉殖株，於遠紅光下幼苗下胚軸比野生型短，CHS基因及花青素含量提升，葉綠素合成受抑制，且短日照下開花時間提早，顯現高度敏感的光形態發生外表型，但在phyA突變體背景中的轉殖株卻無上述表型。由此推測PHYA基因不論N端或C端皆具有傳遞訊息的功能，且須要完整PHYA蛋白質存在才具有作用。phyA is the photoreceptor of far-red light perception in Arabidopsis and mediates the inhibition of the hypocotyl elongation under FR light. phyA has two domains : the N-terminal photosensory domain with a chromophore-binding site and the C-terminal domain which contains signaling motifs such as a kinase domain. FIN219 (far-red insensitive 219) is involved in phytochrome A-mediated inhibition of hypocotyl elongation in FR signaling. Two coiled-coil domains, believed to be involved in protein-protein interactions, are found in FIN219 with one in the N-terminus and the other in the C-terminus. The N-terminal region of FIN219 has 43% similarity at amino acid levels to the GAF domain of PHYA. GH3-10 is a member of the GH3-like gene family in Arabidopsis. Sequence comparison between FIN219 and GH3-10 indicates that there is 47% identity at amino acid level. Hence, we try to understand the functional relationship among FIN219, GH3-10 and phyA to reveal the physiological significance of the similarity. Yeast 2-hybrid interaction studies have revealed that FIN219 can interact with the full length of GH3-10 and the C-terminus of PHYA. Epistatic analysis reveals that FIN219 functions in downstream of the photoreceptor phyA, and its expression is much reduced in the phyA mutant only under FR condition, which suggests that FIN219 function is dependent on the presence of phyA. In addition, the transgenic plants overexpressing the full-length, N- or -C terminal regions of PHYA in wild type background display shorter hypocotyl phenotype as compared to wild type under FR. Other phenotypes such as anthocyanin accumulation, chlorophyll contents, CHS gene expression and flowering time mediated by phyA are consistently enhanced or the same as wild type when N- or -C terminal regions of PHYA are overexpressed in wild type rather than in phyA mutant, which implies that both the N-terminal and the C-terminal domains are functional and able to trigger signal transductions only in the presence of phyA.中文摘要 i 英文摘要 ii 目錄 iv 圖表目錄 vi 縮寫對照表 ix 第一章 前言 1 1. 導論 1 2. 光接受體 1 3. 光訊息的傳導 6 4. GH3基因 10 5. 酵母菌雙雜合法 12 6. 研究目標 12 第二章 材料與方法 14 1. 重組質體之構築 14 2. 酵母菌雙雜合法 14 3. 植物材料與生長條件 15 4. 轉殖株之製備與分析 16 5. 北方墨點法 16 6. 西方墨點法 17 7. 上位性基因的分析（epistatic analysis） 17 第三章 結果 18 1. 重組質體之構築 18 2. LexA酵母菌雙雜合法 18 3. phyA突變體之確認 19 4. FIN219與phyA之間的上位性分析（epistatic analysis） 19 5. 表現FIN219基因於phyA突變體 20 6. 大量表現PHYA全長（PHYA-F:DsRed）、N端（PHYA-N:DsRed）與C端（PHYA-C:DsRed）於野生型和phyA突變體 21 7. p35S:GUS:FIN219和p35S:PHYA:DsRed雜交植株 24 第四章 討論 25 1. FIN219不論N端或C端可能與phyA的C端有蛋白質的交互作用 25 2. FIN219不論N端或C端可能與GH3-10有蛋白質的交互作用….... 28 3. phyA不論N端或C端可能皆具有傳遞訊息的功能 28 4. FIN219可能參與phyA與CP3之間的調控作用 30 第五章 參考文獻 32 第六章 圖表 46 附錄一 實驗方法 85 1. 重組質體之構築 85 2. 酵母菌雙雜合法 91 3. 轉殖株之製備與分析 92 4. 北方墨點法 96 5. 西方墨點法 102 附錄二 一般藥品之配製 108 附錄三 培養藥品之配製 10

Mulberry Leaf Extracts prevent obesity-induced NAFLD with regulating adipocytokines, inflammation and oxidative stress

Mulberry (Morus alba) leaf has been used in Chinese medicine as the remedy for hyperlipidemia and metabolic disorders. Recent report indicated Mulberry leaf extract (MLE) attenuated dyslipidemia and lipid accumulation in high fat diet (HFD)-fed mice. Non-alcoholic fatty liver (NAFLD) is generally considered as the liver component of metabolic syndrome. The hepatic lipid infiltration induces oxidative stress, and is associated with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) which are regulated by the leptin and adiponectin. MLE could prevent obesity-related NAFLD via downregulating the lipogenesis enzymes while upregulating the lipolysis markers. Treatment of MLE, especially at 2%, enhanced the expression of superoxide dismutase (SOD) and clenched the oxidative stress of liver. MLE decreased the plasma level of leptin but increased adiponectin. The advantage of MLE is supposed mainly attributed to chlorogenic acid derivative. We suggest MLE, with promising outcome of research, could be nutraceutical to prevent obesity and related NAFLD. Keywords: Mulberry leaf, Non-alcoholic fatty liver, Adiponectin, Oxidative stress, Inflammatio

Ultrasound Can Be Usefully Integrated with the Clinical Assessment of Nail and Enthesis Involvement in Psoriasis and Psoriatic Arthritis

Objectives: This study aimed to examine and compare the findings of nail and enthesis ultrasonography in patients with psoriasis and psoriatic arthritis. Methods: We identified 154 patients with psoriatic arthritis and 35 patients with psoriasis who were treated at Chang Gung Memorial Hospital, Taiwan, between September 2018 and January 2019. Results: There were significant differences in the Nail Psoriasis Severity Index scores and Glasgow Ultrasound Enthesitis Scoring System scores between patients with psoriasis and those with psoriatic arthritis. B-mode ultrasonography revealed that onychopathic changes were more common in the psoriasis group. The psoriatic arthritis group showed a higher proportion of lower-limb enthesopathy, with significant differences in distal patellar ligament thickness and Achilles tendon thickness. Conclusion: The findings of nail ultrasonography were more severe in psoriasis cases, and the ultrasonographic findings of enthesopathy of the lower limb were more severe in cases of psoriatic arthritis

Extraction of Antioxidant Components from Bidens pilosa Flowers and Their Uptake by Human Intestinal Caco-2 Cells

Bidens pilosa L. var. radiata (BPR, Asteraceae) is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs) and three polyacetylene glucosides (PGAs) to be among the major bioactive markers. To obtain the major compounds of these two chemical classes, the ethyl acetate fraction (EM) obtained using liquid-liquid partition from the methanol extract resulted in a fraction with the highest total phenolic and total flavonoid contents and antioxidant activities in radical scavenging and ferric reducing power assays. To assess the bioavailability of EM, we examined the in vitro uptake using the Caco-2 human colonic cell line. The apparent permeability coefficient (Papp) for each of the compounds within PGAs measured in both apical (AP) to basolateral (BL) and BL to AP was found to preferentially appear BL to AP direction, indicated that a basolateral to apical efflux system was detected in the study. DiCQAs had a lower efflux ratio than those from PGAs (2.32–3.67 vs. 6.03–78.36). Thus, it strongly implies that most of the DiCQAs are better absorbed than the PGAs